This application's long-term objectives are to investigate the histochemical differences between rods and cones and, exploiting these differences, to specify the degenerative changes that occur in human retinal photoreceptor cells with aging and disease. Previous studies revealing histochemical and morphological differences between the blue-sensitive cones and the red- and green sensitive cones will be expanded. Further documentation will be obtained that a sub-population of cones, identified by its absence of carbonic anhydrase (CA) enzymatic activity, is the blue-sensitive cones. Specifically, an attempt will be made to correlate immunocytochemistry for CA with enzyme histochemistry in the human retina. Existing antibodies to putative red/green cones and to blue cones will be compared to CA distribution. Blue cones will also be identified by exposure to vital dyes and to strong spectral lights. The labeled or damaged cones will be compared to CA distribution. Morphological quantitation of the normal anatomical characteristics of blue cones compared to red and green cones will be performed at both the light (LM) and electron microscopic (EM) level. Ultrastructural localization of CA will be employed for the EM studies. The pathogenesis of acquired dyschromatopsia in retinal disease will be studied by examining changes in the morphology and prevalence of the blue cone population versus the red/green cone population in several disorders such as retinal detachment, diabetic retinopathy and glaucoma. Surgical specimens as well as an animal model will be utilized for retinal detachment. Donated eyes with representative stages of diabetic retinopathy will be examined. Glaucoma will be studied with human donor material and an animal model of ocular hypertension. Knowledge gained of the time course of degenerative changes, reversibility of damage and comparative susceptibilities of the four types of photoreceptors may influence accepted approaches to treatment.